Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials
The Lancet Oncology,  Clinical Article

Algra AM et al. – Observational studies show that regular use of aspirin reduces the long-term risk of several cancers and the risk of distant metastasis.

Methods

  • Case—control and cohort studies published from 1950 to 2011 that reported associations between aspirin use and risk or outcome of cancer were searched.
  • Associations were pooled across studies by meta-analysis and stratified by duration, dose, and frequency of aspirin use and by stage of cancer.
  • We compared associations from observational studies with the effect of aspirin on 20-year risk of cancer death and on metastasis in the recent reports of randomised trials.

Results
  • In case—control studies, regular use of aspirin was associated with reduced risk of colorectal cancer (pooled odds ratio [OR] 0·62, 95% CI 0·58—0·67, psig<0·0001, 17 studies), with little heterogeneity (phet=0·13) in effect between studies, and good agreement with the effect of daily aspirin use on 20-year risk of death due to colorectal cancer from the randomised trials (OR 0·58, 95% CI 0·44—0·78, psig=0·0002, phet=0·45).
  • Similarly consistent reductions were seen in risks of oesophageal, gastric, biliary, and breast cancer.
  • Overall, estimates of effect of aspirin on individual cancers in case—control studies were highly correlated with those in randomised trials (r2=0·71, p=0·0006), with largest effects on risk of gastrointestinal cancers (case—control studies, OR 0·62, 95% CI 0·55—0·70, p<0·0001, 41 studies; randomised trials, OR 0·54, 95% CI 0·42—0·70, p<0·0001).
  • Estimates of effects in cohort studies were similar when analyses were stratified by frequency and duration of aspirin use, were based on updated assessments of use during follow-up, and were appropriately adjusted for baseline characteristics.
  • Although fewer observational studies stratified analyses by the stage of cancer at diagnosis, regular use of aspirin was associated with a reduced proportion of cancers with distant metastasis (OR 0·69, 95% CI 0·57—0·83, psig<0·0001, phet=0·89, five studies), but not with any reduction in regional spread (OR 0·98, 95% CI 0·88—1·09, psig=0·71, phet=0·88, seven studies), consistent again with the findings in randomised trials.

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